Influence of Empiric Therapy with a β-Lactam Alone or Combined with an Aminoglycoside on Prognosis of Bacteremia Due to Gram-Negative Microorganisms

Abstract

Evidence supporting the combination of aminoglycosides with ␤-lactams for Gram-negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a ␤-lactam alone versus that with a ␤-lactam-aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative Gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum ␤-lactamase (ESBL)-or AmpC-producing Enterobacteriaceae and Pseudomonas aeruginosa. In patients with Gram-negative bacteremia, we could not find an overall association between empirical ␤-lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy.

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

“…Similar results were achieved in other studies, with mortality in excess of 30% and an increased length of hospital stay related to delays in the initiation of appropriate therapy in ICU patients with sepsis caused by Gram-negative bacteria (84,85,117,136,141,145,152,162). These studies suggest that inappropriate antimicrobial treatment can be reduced with empiric administration of combination therapy.…”

Empiric Combination Therapy for Gram-Negative Bacteremia

“…29,30 These studies further support our conclusion that if a sufficiently broad-spectrum b-lactam agent is selected, in the absence of risk factors for MDRGN organisms, b-lactam monotherapy should be adequate.…”

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

“…Mortality was lower among those patients whose pathogen was sensitive in vitro to either the β-lactam or the aminoglycoside, compared with those whose pathogen was resistant to both (OR, 1.8; 95% CI, 1.3 to 2.5). 76 Nevertheless, and in contrast, an early prospective randomized trial in non-neutropenic patients, in the era prior to the emergence of significant imipenem resistance, showed that the combination of imipenem plus netilmicin was no more efficacious than imipenem monotherapy for the treatment of severe infections, but did have increased nephrotoxicity, and did not prevent the emergence of imipenem-resistant P. aeruginosa. 77 Some in-vitro data suggest synergy in combining two agents against carbapenemase-producing K. pneumoniae, even when the pathogen is resistant to one of these agents.…”